Positron-emission tomography (PET) is a noninvasive and quantitative biomedical imaging approach with applications in early-stage cancer diagnosis, drug discovery, tailoring the treatments for cardiological diseases and neurological disorders. PET is also a powerful tool to monitor disease progression and treatment response. Fluorine-18 (18F)-labelled systems are highly desirable for PET due to the longer half- life of the 18F isotope (110 min) compared to other positron-emitting isotopes. However, due to the lack of sufficient labeling methods, a wide range of molecules cannot currently be labeled with 18F isotope necessary for imaging. Therefore, a high demand exists for more versatile and robust radiochemical methods for incorporation of the 18F isotope into the desired molecules. Fluorine introduction must occur at a late stage of the synthesis, ideally in the last step, to avoid unproductive decay of the 18F radionucleus before injection into the body. Conventional fluorination reactions often cannot afford complex PET tracers because they do not tolerate the functional groups commonly present in PET tracers; or the reactions typically take a long time which is not within the time scale 18F short half-life. We recently found a new reagent and a new reaction to incorporate 18F into molecules which solved the long-standing problem of labeling electron-rich and neural phenols which are abundant in many PET tracers. The objectives of this proposal are 1. to use nanotechnology for the first time in PET tracer synthesis and prepare epitaxially grown metal-organic frameworks (MOFs) thin films as enzyme mimetics in tandem late stage 18F-fluorination. MOFs are crystalline hybrid materials with nanoreactor environment which allow us to incorporate two functional components in them, so a two-step reaction in one pot will be enabled to save time due to 18F short half-life. 2. To apply these new MOF materials in PET chemistry and prepare challenging PET tracers. While the first component of MOF thin films can readily capture the 18F from cyclotron as a sensor, the second component will enable the chemical catalysis and provide the PET tracer product in a tandem fashion. Doing two steps in one pot makes our proposed approach to be much faster than the conventional methods at least by one order of magnitude and functional group tolerant. The long-term goal of this project is to translate our technology in the labeling of peptides. Four peptides have been proposed to start with and then we will expand our methods towards larger peptides such as insulin which will reveal interesting information of the associated diseases and syndromes. In summary, we propose here reaction development to enable practical, readily performed methodologies for PET probes synthesis that are challenging to achieve. The optimization of reactions will be followed by a mechanism-based approach. We will showcase the generality and utility of our new methodologies by the preparation of several radiotracers that are challenging to synthesize with conventional approaches.